Studies on the relation between the biological function and the dynamic properties of rat liver plasma and microsomal membranes

大鼠肝血浆及微粒体膜生物学功能与动态特性关系的研究

• 批准号: 60571057
• 负责人: UTSUMI Hideo
• 金额: $ 1.09万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60571057/
• 关键词: rat liver microsomes; spin-label; ESR; biomembrane; phenobarbirtal; cytochrome P-450; フェノバルビタール; 生体膜

To elucidate the relation between the cellular function and the dynamic properties of biomembranes, we studied the membrane fluidity and nitroxide reduction activity of rat liver microsomes with spin-label technique.1. Four spin-labeled stearic acids were used as both probes for membrane fluidity and substrates for nitroxide reduction by NADPH cytochrome P-450 reductase - cytochrome P-450 system. Active center of nitroxide reduction of microsomes was found to locate around 7-12 carbon position of stearic acid in membranes. The nitroxide reduction was induced by the administration of phenobarbital but not by 3-methylcholanthrene. However, the membrane fluidity of liver microsomes increased by the administration of phenobarbital, polychlorinated biphenyls or 3-methylcholanthrene.2. Oral administration of C <Cl_4> , CH <Cl_3> , CH <Br_3> and CH <Br_2> Cl changed membrane structure and nitroxide reduction activity of rat liver microsomes. ESR spectrum of methyl ester of spin-labeled steari … More c acid in microsomes showed the presence of non-bilayer and bilayer phases in membranes. The transfer rate of the spin probes between two phases was changed by the oral administration of these compounds. Nitroxide reduction rate also decreased by the treatment. Among these compounds, C <Cl_4> gave the most influence on the membrane fluidity and nitroxide reduction.3. In vitro treatment of C <Cl_4> and CH <Br_3> to rat liver microsomes caused lipid peroxidation of microsomal membranes in addition to decrease of cytochrome P-450 contents, arylesterase and demethylase activity when NADPH generating system was added, but not in the absence of the system. These compounds increased the membrane fluidity of liver microsomes, while the metabolites of the compounds decreased. Nitroxide reduction activity of microsomes also decreased by the compounds themselve, but much decrease was observed in the presence of NADPH generating system.4. Long-term administration of phenobarbital to rat caused significant decrease of the activity in drug metabolizing enzymes. Less

为了阐明细胞功能与生物膜动力学性质之间的关系，我们用自旋标记技术研究了大鼠肝微粒体的膜流动性和氮氧自由基还原活性.用四种自旋标记的硬脂酸作为细胞膜流动性的探针和NADPH细胞色素P-450还原酶-细胞色素P-450系统还原氮氧自由基的底物。微粒体氮氧自由基还原活性中心位于膜中硬脂酸的7-12碳位。氮氧自由基的减少是由苯巴比妥的管理，但不是由3-甲基胆蒽。而苯巴比妥、多氯联苯和3-甲基胆蒽可使肝微粒体膜流动性增加.口服C<Cl_4>、CH<Cl_3>、CH<Br_3>和CH <Br_2>Cl改变了大鼠肝微粒体的膜结构和氮氧自由基还原活性。自旋标记硬脂酸甲酯的ESR谱 ...更多信息 微粒体中的C酸显示膜中存在非双层和双层相。通过口服这些化合物改变了两相之间自旋探针的转移速率。处理后氮氧化物还原率也有所下降。在这些化合物中，C<Cl_4>对膜流动性和氮氧自由基还原的影响最大.在体外实验中，C<Cl_4>和CH<Br_3>对大鼠肝微粒体的作用除了引起细胞色素P-450含量、芳香酯酶和脱甲基酶活性的降低外，还引起微粒体膜脂质过氧化反应。这些化合物增加肝微粒体的膜流动性，而化合物的代谢产物减少。化合物本身也能降低微粒体的氮氧自由基还原活性，但在NADPH生成系统存在下，其活性下降幅度更大.大鼠长期服用苯巴比妥可引起药物代谢酶活性明显降低。少

项目成果

Jun-Ichiro Murayama, Hideo Utsumi and Akira Hamada: "Effect of CH <Br_3> and CH <Br_2> Cl on rat liver microsomal membranes by oral administration. Spin-label studies"

Jun-Ichiro Murayama、Hideo Utsumi 和 Akira Hamada：“CH <Br_3> 和 CH <Br_2> Cl 通过口服给药对大鼠肝微粒体膜的影响。自旋标记研究”

Kayoko Fukuda, Akira Shimakura, Hideo Utsumi and Akira Hamada: Structural and enzymatic changes of rat liver microsomal membranes by the hepatotoxic actions of halogenomethanes,

Kayoko Fukuda、Akira Shimakura、Hideo Utsumi 和 Akira Hamada：卤代甲烷的肝毒性作用对大鼠肝微粒体膜的结构和酶促变化，

Hideo Utsumi, Akira Shimakura and Akira Hamada: "Location of active center of nitroxide reduction in rat liver microsomes and its membrane fluidity - The effect of typical inducers" SUBMITTED.

Hideo Utsumi、Akira Shimakura 和 Akira Hamada：“大鼠肝微粒体中氮氧化物还原活性中心的位置及其膜流动性 - 典型诱导剂的作用”已提交。

Hideo Utsumi;Jun-Ichiro Murayama;Kayoko Fukuda;Akira Hamada: 31. P-29- (1985)

内海秀夫；村山淳一郎；福田佳代子；滨田晃：31. P-29- (1985)

Hideo Utsumi, Jun-Ichiro Murayama, Kayoko Fukuda and Akira Hamada: "Effect of organic halogen compounds on the structure and reductase activity of rat liver microsomal membranes (II)" Eisei Kagaku. 31. (1985)

Hideo Utsumi、Jun-Ichiro Murayama、Kayoko Fukuda 和 Akira Hamada：“有机卤素化合物对大鼠肝微粒体膜结构和还原酶活性的影响（II）”Eisei Kagaku。